Tuning the allosteric sequestration of anticancer drugs for developing cooperative nano-antidotes

Abstract

A dual-cavity basket 1⁶⁻, holding six γ-aminobutyric acids at its termini, encapsulates variously sized aromatics 2–7⁺, including four anthracyclines (8⁺–11⁺), driven by the hydrophobic effect and hydrogen bonding (HB). In particular, the formation of stable (K = 10¹² M⁻²) anthracycline complexes [(8⁺–11⁺)₂⊂1⁶⁻], assembled into nanoparticles, occurred with positive homotropic cooperativity (α = 4K₂/K₁ = 1.1 ± 0.3 × 10²–1.3 ± 0.7 × 10³) in PBS medium. Importantly, weakening the first binding event (K₁, i.e. by removing HBs) turned the second one (K₂) more favorable. The finding is of interest for developing cooperative nano-antidotes acting as biodetoxifying agents.